Thus, a new cell line, BEL-A (Bristol Erythroid Line Adult), was created. bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes. (var. gene inside cells (the phenylalanine-ammonia lyase gene Anabaena variabilis), is being conducted to treat adult phenylketonuria (“type”:”clinical-trial”,”attrs”:”text”:”NCT04110496″,”term_id”:”NCT04110496″NCT04110496) [239]. At conferences in Philadelphia and Boston in 2019, Zhang [240] and Moore [241] proposed interesting ideas for creating artificial antigen-presenting cells, the genetically modified erythrocytes (RCT-aAPC), which expresses immunomodulating signals that are directed against the tumor. Such cells, on the one hand, are loaded with tumor-specific antigen and costimulatory molecules, and, on the other hand, express proteins of the main histocompatibility class I complex on the surface to create an effective tumor-specific T-cell response. Using this strategy in mice showed 60% inhibition of tumor growth on day 7 after administration of RCT-aAPC to animals. Thus, RubiusTherapeutics technology represents a new promising approach for the delivery of therapeutic substances to patients using erythrocytes. These results are QX77 especially encouraging in light of the fact that, in 2017, a method was developed to create an immortal line of erythrocytes from the corresponding erythrocyte precursors [242]. If you have a QX77 culture of unipotent erythrocyte precursors, you do not need to worry about managing their Eptifibatide Acetate differentiation. However, unlike stem cells, the number of divisions of such cells is limited; thus, they must be immortalized, i.e., modified so that their division can be endless. For this, bone marrow, cells were genetically modified by adding a human papilloma virus gene to them, QX77 which allows cells to divide unlimitedly. Then, the transition of the modified cells into erythrocyte precursor cells was induced. Thus, a new QX77 cell line, BEL-A (Bristol Erythroid Line Adult), was created. The course of these cells differentiation did not differ from the corresponding stages of development of pluripotent stem cells. The results obtained appear promising for the possibility of scaling the process to obtain the desired RBCs in sufficient quantities. 7. Limitations of the RBCs Use as Drug Carriers Despite the fact that RBCs are very promising for use as drug carriers, their use has a number of limitations. The source of RBCs is blood; thus, the use of allogeneic blood can lead to errors in choosing the right blood type and to the transmission of various infections. However, these disadvantages are common to all transfusion of blood products. These situations are very rare, and currently they are not the principal barrier to transfusion of any blood products, including erythrocytes loaded with drugs. In addition, production of carrier erythrocytes are associated with the need for sterile work and the complexity of the large-scale production of such cells. Creating automatic devices can solves these problems. Another disadvantage is related to the fact that if any crude method was used for CEs preparation, the quality of the resulting cells may not be high enough. In this case, these CEs will rapidly degrade in the bloodstream, and the drug may be released uncontrollably. This complicates drug delivery and can lead to adverse side effects. However, the methods currently used are soft enough and do not have a strong effect on RBCs. There are also other restrictions. The first of them is that far from any substance can be incorporated into RBCs. Some low molecular weight compounds that easily pass through the erythrocyte membrane are not only easy to enter, but also just as easy to leave QX77 the cells, which makes it impossible to create a long-term depot form of these compounds based on RBCs in the bloodstream [82,94,140]. To slow the release of such substances from RBCs, the cells may be treated with different crosslinking agents (primarily for NH2C or HSC groups on the.